Structure-Function Insights into Anionic and Cationic Undecapeptides: A Combined Modeling and Antibacterial Study

Antimicrobial peptides (AMPs) represent a promising class of alternatives to conventional antibiotics. In this study, we compared the structural and functional properties of three synthetic undecapeptides: the anionic Cn-AMP2 and its N-terminally acetylated derivative (Ac-CnAMP2), versus the cationic α-helical peptide BP52. While BP52 exhibited strong antibacterial activity against both Gram-positive and Gram-negative bacteria, Cn-AMP2 and Ac-CnAMP2 showed no measurable antibacterial effects up to 128µM. Hemolysis assays revealed that BP52 caused mild to moderate lysis of red blood cells, whereas the anionic peptides were non-hemolytic. Molecular dynamics simulations confirmed the enhanced membrane insertion, clustering behavior, and bilayer disruption induced by BP52, in contrast to the limited interaction profiles of Cn-AMP2. These findings underscore the importance of positive charge, helical conformation, and amphipathic topology in driving membrane action and offer insights for designing optimized AMP-based therapeutics.